Effect of sesamin and related compounds on adipocyte differentiation and PPARγ transcriptional activity

Autor: Wang, Yun-Chi, 王韻琪
Rok vydání: 2017
Druh dokumentu: 學位論文 ; thesis
Popis: 105
The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear transcription factor activated by ligands. PPARγ plays an important role in adipocyte differentiation and in the regulation of glucose and fat metabolism. When the ligands bind to PPARγ ligand binding site, it can affect glucose uptake and improve insulin sensitivity in type 2 diabetes. There are many PPARγ full agonists clinically used to counteract hyperglycemia, but they have serious side effect, such as weight gain and hepatotoxicity. Partial agonists from natural products have been demonstrated to retain anti-metabolic syndrome effect and reduced side effects in comparison to full thiazolidinedione agonists. The purpose of this study was to investigate the effects of sesamin and its derivatives (SD1 and SD4) on adipocyte differentiation and PPARγ activation. Competitive time-resolved fluorescence resonance energy transfer (TR-FRET) assays confirmed that sesamin and its derivatives (SD1 and SD4) were directly bound to PPARγ ligand binding domain (LBD).A luciferase reporter assay demonstrated that sesamin and its derivatives induced transcriptional activation of PPARγ through binding to the PPRE enhancer sequence. In 3T3-L1 cells, sesamin, SD1 and SD4 stimulated adipogenic differentiation in a dose-dependent manner. These results indicated that sesamin and its derivatives served as PPAR agonist and exert adipocyte differentiation in 3T3-L1 cells through PPARγ activation.
Databáze: Networked Digital Library of Theses & Dissertations